公开(公告)号：US07700560B2

公开(公告)日：2010-04-20

申请号：US10559410

申请日：2004-05-28

申请人： Donald J. Creighton ,  Zhe-Bin Zheng

发明人： Donald J. Creighton ,  Zhe-Bin Zheng

IPC分类号： A61K38/08 ,  C07K5/02 ,  C07K5/08 ,  C07K5/10

CPC分类号： C07K7/02 ,  A61K38/00 ,  A61K47/55 ,  A61K47/60 ,  A61K47/64 ,  C07K5/0202 ,  C07K5/0215

摘要： Compounds comprising two human GlxI inhibitors covalently linked via a chemical linker are provided, wherein each of said two human GlxI inhibitors, which may be the same or different, is an S-substituted glutathione or an S-substituted glutathione prodrug, wherein said GlxI inhibitors each have a γ-glutamyl amino group, wherein said chemical linker is covalently bound to each GlxI inhibitor via said γ-glutamyl amino group, and wherein said chemical linker has a length of at least 50 Angstroms. Monovalent irreversible inactivators of human GlxI are also provided. An antineoplastic composition is provided, which comprises a compound described above and a pharmaceutically acceptable carrier. In vitro and in vivo methods of preventing or inhibiting the growth and proliferation of neoplastic cells and/or tumors are also provided.

摘要翻译： 提供了包含通过化学接头共价连接的两个人GlxI抑制剂的化合物，其中所述两种可以相同或不同的人类GlxI抑制剂中的每一种都是S-取代的谷胱甘肽或S-取代的谷胱甘肽前药，其中所述GlxI抑制剂 每个具有γ-谷氨酰氨基，其中所述化学连接体经由所述γ-谷氨酰氨基共价结合到每个GlxI抑制剂，并且其中所述化学连接体具有至少50埃的长度。 还提供了人GlxI的单价不可逆灭活剂。 提供抗肿瘤组合物，其包含上述化合物和药学上可接受的载体。 还提供了预防或抑制肿瘤细胞和/或肿瘤的生长和增殖的体外和体内方法。

公开(公告)号：US07569711B2

公开(公告)日：2009-08-04

申请号：US11006132

申请日：2004-12-07

申请人： Bruce Ganem ,  Donald J. Creighton ,  Diana S. Hamilton ,  Zhebo Ding

发明人： Bruce Ganem ,  Donald J. Creighton ,  Diana S. Hamilton ,  Zhebo Ding

IPC分类号： C07C59/147 ,  C07C59/185 ,  C07C315/00 ,  C07C317/00

CPC分类号： A61K31/56 ,  A61K38/00 ,  C07K5/0215

摘要： Described herein are new enone derivatives and conjugates. Additionally, methods for synthesizing these new enones are also disclosed. These compounds can be employed in cancer therapy.

摘要翻译： 本文描述的是新的烯酮衍生物和共轭物。 此外，还公开了合成这些新的烯酮的方法。 这些化合物可用于癌症治疗。

公开(公告)号：US5616563A

公开(公告)日：1997-04-01

申请号：US264940

申请日：1994-06-24

申请人： Donald J. Creighton ,  Diana S. Hamilton

发明人： Donald J. Creighton ,  Diana S. Hamilton

IPC分类号： C07C333/12 ,  A61K38/06

CPC分类号： C07C333/12

摘要： A compound of the formula ##STR1## with R being hydrogen, alkyl, cycloalkyl or aryl, which may be substituted with halogen or alkyl, and R' and R.sup.a being hydroxyl, or --O-alkyl, pharmaceutically acceptable salts thereof; or mixtures thereof. An anti-neoplastic composition comprises the compound described above and a pharmaceutically acceptable carrier. In vitro and in vivo methods of preventing or inhibiting the growth and proliferation of neoplastic cells and/or tumors comprise contacting the cells with or administering to a subject an anti-growth and proliferation effective amount of the compound described above.

摘要翻译： 式（I）的化合物，其中R为氢，烷基，环烷基或芳基，其可被卤素或烷基取代，R'和R a为羟基或-O-烷基，其药学上可接受的盐; 或其混合物。 抗肿瘤组合物包含上述化合物和药学上可接受的载体。 预防或抑制肿瘤细胞和/或肿瘤的生长和增殖的体外和体内方法包括使细胞与受试者接触抗生长和增殖有效量的上述化合物。